目的：研发0.1 mg/mL的肾上腺素注射液，建立相应的低浓度肾上腺素注射液质量控制方法并进行了中试研究，解决一些低浓度肾上腺素注射液关键技术的难点问题。

方法：使用高效液相色谱法对肾上腺素注射液中肾上腺素的含量、有关物质、异构体含量进行测定；剖析肾上腺素的理化性质，对pH、焦亚硫酸钠用量和注射液中溶解氧水平进行处方筛选，通过其稳定性试验结果数据，确定出处方；对充氮工艺、原辅料加入顺序和灭菌工艺研究进行工艺筛选，通过其稳定性试验数据，确定工艺；建立肾上腺素注射液质量评价系统，采用最适处方和最适工艺制备注射液，并进行中试以及后续质量评价和稳定性研究。

结果：建立了低浓度肾上腺素注射液相关降解杂质的有关物质分析方法，建立了含量、异构体及焦亚硫酸钠含量的分析方法。确定低浓度肾上腺素注射液处方为肾上腺素1.0 mg、焦亚硫酸钠4.6 mg、氯化钠81.6 mg、无水枸橼酸21.3 mg、枸橼酸钠二水合物4.1 mg，加水至10 mL。溶解氧应控制在0~1.3 ppm，pH控制在2.9~3.1，中试产品制备过程充氮不会对pH造成明显变化，中试产品稳定性良好。

结论：建立了低浓度肾上腺素注射液质量分析方法，通过处方和工艺优化，制备出稳定的低浓度肾上腺素注射液，进行了中试产品的制备并通过相应的质量评价，解决了低浓度肾上腺素注射液关键技术的一些难点问题。

目的：构建益生元为载体的阿托伐他汀（Atorvastatin, AT）固体分散体以增加AT治疗非酒精性脂肪性肝病(Non-alcoholic Fatty Liver Disease NAFLD)作用。

方法：本课题以菊粉（Inulin, GR）为载体材料，乙醇为溶剂，采用溶剂挥发法制备了阿托伐他汀（AT）固体分散体并对其进行表征；建立体外溶出度和含量检测方法并进行分析方法学验证；确定固体分散体中阿托伐他汀的含量，并对AT制剂进行体外溶出实验；构建高脂饮食诱导C57小鼠非酒精性脂肪性肝病模型，对AT制剂进行体内药效学评价及肠道菌群分析。

结果：成功制备阿托伐他汀-菊粉固体分散体（AT-GR）；体外溶出试验表明AT-GR在纯水中的溶出速率显著高于AT原药；在高脂饮食（HFD）喂养的C57小鼠中，AT-GR干预有效地重建了肠道微生物群。此外，与AT相比，AT-GR治疗显著抑制体重增加和脂肪沉积，降低血脂水平，减轻肝脏脂肪变性。

结论：AT-GR可增加AT的溶出速率，同时有效改善高脂饮食引起的肠道菌群紊乱，从而增加AT治疗NAFLD作用。

Objective: Develop 0.1 mg / ml Adrenaline injection, establish the corresponding quality control method of low concentration Adrenaline injection, and conduct pilot study to solve some key technical difficulties of low concentration Adrenaline injection.

Methods: The contents of Adrenaline, related substances and isomers in Adrenaline injection were determined by HPLC; Analyze the physical and chemical properties of Adrenaline, screen the prescription of pH, the dosage of sodium pyrosulfite and the dissolved oxygen level in the injection, and determine the prescription through the data of its stability test results; The nitrogen filling process, the addition sequence of raw and auxiliary materials and the sterilization process are screened, and the process is determined through its stability test data; Establish the quality evaluation system of Adrenaline injection, prepare the injection with the optimal prescription and process, and conduct pilot test, follow-up quality evaluation and stability study.

Results: The analytical method of related substances related to degradation impurities of low concentration Adrenaline injection was established, and the analytical methods of content, isomer and sodium pyrosulfite were established. The prescription of low concentration Adrenaline injection was determined as Adrenaline 1.0 mg, sodium pyrosulfite 4.6 mg, sodium chloride 81.6 mg, anhydrous citric acid 21.3 mg, sodium citrate dihydrate 4.1 mg, and water was added to 10 ml. The dissolved oxygen shall be controlled at 0 ~ 1.3 ppm and the pH shall be controlled at 2.9 ~ 3.1. The nitrogen filling in the preparation process of the pilot product will not cause significant changes to the pH, and the pilot product has good stability.

Conclusion: The quality analysis method of low concentration Epinephrine injection was established. Through the optimization of prescription and process, a stable low concentration Epinephrine injection was prepared, and the pilot product was prepared. Through the corresponding quality evaluation, the key technical difficulties of the industrialization of low concentration Epinephrine injection were solved.

Objective: The solid dispersion of Atorvastatin (AT) with prebiotic as carrier was constructed to increase the effect of at in the treatment of Nonalcoholic Fatty Liver Disease(NAFLD).

Methods: In this study, AT solid dispersion was prepared and characterized by solvent volatilization method with inulin (GR) as carrier material and ethanol as solvent; The dissolution and content determination methods in vitro were established and verified by analytical methodology; The content of AT in solid dispersion was determined, and the dissolution experiment of AT preparation was carried out in vitro; The model of NAFLD in C57 mice induced by High-Fat Diet (HFD) was established, and the in vivo pharmacodynamics and intestinal flora of AT preparation were evaluated.

Results: AT-GR solid dispersion was successfully prepared; In vitro dissolution test showed that the dissolution rate of AT-GR in pure water was significantly higher than that of AT technical drug; In C57 mice fed HFD, AT-GR intervention effectively reconstructed the intestinal microbiota. In addition, compared with AT, AT-GR treatment significantly inhibited weight gain and fat deposition, reduced blood lipid level and reduced hepatic steatosis.

Conclusion: At-GR can increase the dissolution rate of at and effectively improve the intestinal flora disorder caused by HFD, so as to increase the effect of at in the treatment of NAFLD.